TY - JOUR
T1 - The complexation between novel comb shaped amphiphilic polyallylamine and insulin
T2 - towards oral insulin delivery
AU - Thompson, C.
AU - Tetley, L.
AU - Uchegbu, I.F.
AU - Cheng, W.P.
N1 - Original article can be found at : http://www.sciencedirect.com/ Copyright Elsevier [Full text of this article is not available in the UHRA]
PY - 2009
Y1 - 2009
N2 - Novel amphiphilic polyallylamine (PAA) were previously synthesised by randomly grafting palmitoyl pendant groups and subsequent quaternising with methyl iodide. The ability of these self-assembled polymers to spontaneously form nano-complexes with insulin in pH 7.4 Tris buffer was evaluated by transmittance study, hydrodynamic size and zeta potential measurements. The transmission electron microscopy images showed that non-quaternised polymer complexes appeared to form vesicular structures at low polymer:insulin concentrations. However, at higher concentrations they formed solid dense nanoparticles. The presence of quaternary ammonium moieties resulted in insulin complexing on the surface of aggregates. All polymers exhibited high insulin complexation efficiency between 78 and 93%. Incubation with trypsin, α-chymotrypsin and pepsin demonstrated that most polymers were able to protect insulin against enzymatic degradation by trypsin and pepsin. Quaternised polymers appeared to have better protective effect against trypsinisation, possibly due to stronger electrostatic interaction with insulin. Interestingly, non-quaternised polymers significantly enhanced insulin degradation by α-chymotrypsin. All polymers were less cytotoxic than PAA, with the quaternised polymers exhibiting up to 15-fold improvement in the IC50 value. Based on these results, quaternised palmitoyl graft polyallylamine polymers showed promising potential as oral delivery systems for insulin.
AB - Novel amphiphilic polyallylamine (PAA) were previously synthesised by randomly grafting palmitoyl pendant groups and subsequent quaternising with methyl iodide. The ability of these self-assembled polymers to spontaneously form nano-complexes with insulin in pH 7.4 Tris buffer was evaluated by transmittance study, hydrodynamic size and zeta potential measurements. The transmission electron microscopy images showed that non-quaternised polymer complexes appeared to form vesicular structures at low polymer:insulin concentrations. However, at higher concentrations they formed solid dense nanoparticles. The presence of quaternary ammonium moieties resulted in insulin complexing on the surface of aggregates. All polymers exhibited high insulin complexation efficiency between 78 and 93%. Incubation with trypsin, α-chymotrypsin and pepsin demonstrated that most polymers were able to protect insulin against enzymatic degradation by trypsin and pepsin. Quaternised polymers appeared to have better protective effect against trypsinisation, possibly due to stronger electrostatic interaction with insulin. Interestingly, non-quaternised polymers significantly enhanced insulin degradation by α-chymotrypsin. All polymers were less cytotoxic than PAA, with the quaternised polymers exhibiting up to 15-fold improvement in the IC50 value. Based on these results, quaternised palmitoyl graft polyallylamine polymers showed promising potential as oral delivery systems for insulin.
KW - polymeric self-assemblies
KW - nano-complexes
KW - enzymatic degradation
U2 - 10.1016/j.ijpharm.2009.04.014
DO - 10.1016/j.ijpharm.2009.04.014
M3 - Article
SN - 0378-5173
VL - 376
SP - 46
EP - 55
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
IS - 1-2
ER -